System, tools, devices and a program for diabetes care

ABSTRACT

A method for diabetes care, the method (which also may be referred to as, involve or incorporate at least one of a tool, device or program) allowing for the characterization of the relevance of errors of parameters affecting glucose concentration on a postprandial glucose concentration outcome for a person with diabetes mellitusm, wherein the method involves at least one of sensing, determining, calculating, predicting, describing and communicating the effects of potential errors of parameters affecting glucose concentration on postprandial glucose concentration values within a clinically relevant glucose range.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/CH2006/000483, filed on Sep. 8, 2006, which claims priority toSwiss Application No. 1468/05, filed on Sep. 9, 2005, the contents ofwhich are hereby incorporated in their entirety by reference herein.

BACKGROUND

The present invention relates to the treatment or therapeutic care ofdiabetes, to devices for use in diabetes care, and to methods of makingand using such devices, and to methods of treatment or care of diabetes.In some embodiments, the present invention relates to at least one of asystem, a diagnostic tool, a therapeutic tool and an educational toolfor diabetes self-management. In some embodiments, the present inventionrelates to a medical device for use in diabetes care, e.g. a bloodglucose meter, an insulin pump or a continuous glucose monitoringdevice. In some embodiments, the present invention relates to program,method or process for diabetes management, and to a data carrierincluding such a program.

Considerable progress has been made in the development of diagnostic,therapeutic and educational tools for diabetes self-management. However,it is less recognized that in the daily life of people with diabetesmellitus all such tools are characterized by rather large and varyingmargins of error. There exists insufficient knowledge about the effectsof such errors on postprandial blood glucose and, thus, about theircontribution to the increases risk of hypoglycemia and hyperglycemia.

Some currently known systems, and in particular systems for continuousglucose monitoring, do not display actual results to avoid a possiblyfalse therapy decision based on an uncertain measuring value (a valuewith a measuring error that could be too large). With such systems onlya retrospective analysis of the measured values is possible.[Mastrototaro J. The MiniMed Continuous Glucose Monitoring System.Journal of Pediatric Endocronology & Metabolism, 12, 751-758 (1999)].

Other systems for continuously monitoring glucose do display actualmeasurement values, but are not approved for therapy decisions. For suchdecisions it is in both cases necessary to measure the blood glucosevalue with strip measurement devices. [FDA Approval order GlucoWatchAutomatic Glucose Biographer-P990026,http://www.fda.gov/cdrh/pdf/p990026.html].

According to the manufacturer's information a system for continuousglucose monitoring shall be able to allow therapy decision withoutconfirmaton by a conventional measuring system. [Feldman B, Brazg R,Schwartz S, Weinstein R. A Continuous Glucose Sensor Based on WiredEnzyme Technology. Diabetes Technology & Therapeutics, 5, 5, 769-779,2003].

SUMMARY

One object of the present invention is to provide a system that allows aperson with diabetes or a medical practioner or caregiver to predict apostprandial blood glucose value. Another object of the presentinvention is to provide a model for explaining the impacts of errors ofmeasurements and estimations in diabetes treatment and diabetes selfcare. Another object of the present invention is to provide devices thatallow a more precise prediction of postprandial blood glucose and, thus,can give valid treatment information and/or advice.

To implement these and other objects of the present invention, whichwill become more readily apparent as the description proceeds, thepresent invention is manifested by a system for determining postprandialblood glucose taking into account factors or variables in the treatmentof diabetes, including one or more of the following:

-   -   preprandial blood glucose measurement by self-monitoring of        glucose,    -   the effect of carbohydrate-portion on maximum glucose incrase,    -   an estimate of carbohydrate amount in meal,    -   the effect of preprandial insulin on maximum glucose decrease,        and    -   insulin dosage,        wherein a margin of error for self-monitored preprandial glucose        is taken into account and postprandial glucose values are        calculated based on a therapeutic action scheme.

In one embodiment, the present invention comprises a method (which alsomay be referred to as, involve or incorporate a system, tool, device orprogram) for diabetes care, the method allowing for the characterizationof the relevance of errors of parameters affecting glucose concentrationon a postprandial glucose concentration outcome for a person withdiabetes mellitusm, wherein the method involves at least one of sensing,determining, calculating, manipulating, predicting, describing andcommunicating the effects of potential errors of parameters affectingglucose concentration on postprandial glucose concentration valueswithin a clinically relevant glucose range.

In one embodiment, the present invention comprises a method of therapy,diagnosis or education involving postprandial glucose concentration,said method comprising the step of taking into account at least one of apreprandial glucose measurement by self-monitoring of glucoseconcentration, an effect of carbohydrate-portion on maximum glucoseincrease, an estimate of carbohydrate amount in a meal, an effect ofprandial insulin on maximum glucose decrease, and an insulin dosage,wherein a margin of error for self-monitored preprandial glucose istaken into account and postprandial glucose values are calculated basedon a therapeutic action scheme. In some embodiments, the invention mayfurther comprise the step of taking into account an error associatedwith at least one of the effect of carbohydrate-portion on maximumglucose increase, the estimate of carbohydrate amount in a meal, theeffect of prandial insulin on maximum glucose decrease, and the insulindosage. In some embodiments, the invention may comprise determining thepostprandial blood glucose for different ranges of preprandial glucoseconcentration values according to the therapeutic scheme, andcommunicating a result as postprandial glucose over preprandial glucose.In some embodiments, it is determined whether a critical point isreached by exceeding a lower limit for glucose concentration or byexceeding an upper limit for glucose concentration.

In some embodiments of the methods in accordance with the presentinvention, the therapeutic scheme includes a carbohydrateself-adjustment in relation to preprandial glucose concentrationaccording to the relation:

Glucose (mg/dl)<40 40-60 61-120 121-160 161-200 201-240 241-300 301-360CARB-P (n) X+2 X+1 X X−1 X−2 X−3 X−4 X−5 wherein X equals the number ofcarbohydrate portions (X=1, 2, 3, 4 or 5) for the glucose-range of61-120 mg/dl.

In some embodiments, the method comprises a therapeutic scheme includesa pre-prandial insulin dose self-adjustment according to the relation:

BG (mg/dl)<61 61-80 81-120 121-160 161-200 201-240 241-300 301-360Ins.-Dose (U) 0 −1Y Y +1Y +2Y +3Y +4Y +5Y wherein Y equals e.g. 1 unitinsulin per 1 CARB-P for the blood glucose range of 81-120 mg/dl.

In some embodiments, the trend of a continuous glucose monitoring isconsidered as follows:

Glucose (mg/dl) Trend <61 61-80 81-120 121-160 161-200 201-240 241-300301-360 UU 0   Y +1Y +2Y +3Y +4Y +5Y +6Y U 0 −1Y   Y +1Y +2Y +3Y +4Y +5Y= 0 −1Y   Y +1Y +2Y +3Y +4Y +5Y D 0 −2Y −1Y   Y +1Y +2Y +3Y +4Y DD 0 −3Y−2Y −1Y   Y +1Y +2Y +3Yand wherein the trends are defined as follows

Very Fast glucose increase >+2 mg/dl/min UU Fast +(1-2) mg/dl/min U Slowchanges <±1 mg/dl/min = Fast decrease −(1-2) mg/dl/min D Very Fastdecrease >−2 mg/dl/mim DD

In some embodiments of the method in accordance with the presentinvention, the method may involve or be carried out or performed by orin conjunction with at least one of a blood glucose meter, an insulinpump or a continuous glucose monitor.

In some embodiments, the system or tool (or method) of the presentinvention has been developed and/or is adapted to evaluate the effectsand the clinical relevance of the margins of error of parametersaffecting glucose. In some embodiments, it is based on a diabetestreatment concept aimed at normoglycemia after meals by preprandialinjections of insulin. The system or tool includes as parameters one ormore of: a) preprandial measurement, b) effect of carbohydrate portions(CARE-P) on maximum glucose increase, c) patient estimate ofcarbohydrate amounts in food, d) effect of insulin on maximum glucosedecrease, and e) insulin dosage. The invention analyzes (for example in1 mg/dl steps) the maximum effect of the above parameters (including themargins of error of at least the parameter of preprandial measurement)on postprandial glucose. In some preferred embodiments involving theclinically relevant range of preprandial blood glucose values (30-330mg/dl), the system simulates the postprandial blood glucose values asoutcomes according to a treatment algorithm in adult persons withdiabetes. If a postprandial outcome is not normoglycemia, but turns intohyperglycemia or hypoglycemia, a critical point (CP) can be evaluated.

Any of the above-noted parameters or factors can induce a CP ofpostprandial blood glucose if they reach a specific margin of error. Thepresent invention, in any of its forms, relates to glucose measurementor glucose monitoring in any tissue compartment, tissue and body fluid,e.g. interstitial fluids where such measurement or monitoring ispossible. Some preferred embodiments of the present invention involvethe measurement of blood glucose and, in the examples described herein,said measurement of blood glucose may be assumed unless otherwisestated.

In some embodiments, the present invention is manifested by at least oneof a therapeutic tool, a diagnostic tool and an educational tool,wherein the tool(s) includes as parameters one or more of: a)preprandial measurement, b) effect of carbohydrate portions (CARB-P) onmaximum glucose increase, c) patient estimate of carbohydrate amounts infood, d) effect of insulin on maximum glucose decrease, and e) insulindosage. The tool analyzes (for example in 1 mg/dl steps) the maximumeffect of the above parameters including the margins of error at leastof the parameter preprandial glucose on postprandial glucose. In somepreferred embodiments, one or several of the other parameters are aswell considered with their margins of error. In some preferredembodiments, covering the clinically relevant range of preprandial bloodglucose values (30-330 mg/dl), the tool simulates the postprandial bloodglucose values as outcome according to a treatment algorithm.

In some embodiments, the present invention is further manifested by adevice, e.g. a blood glucose meter, a continuous glucose monitor or aninsulin pump, wherein the device operates and/or determines postprandialglucose by including as parameters one or more of: a) preprandialmeasurement, b) effect of carbohydrate portions (CARB-P) on maximumblood glucose increase, c) patient estimate of carbohydrate amounts infood, d) effect of insulin on maximum glucose decrease, and e) insulindosage. The device analyzes (for example in 1 mg/dl steps) the maximumeffect of the above parameters, including the margins of error at leastof the parameter preprandial glucose, on postprandial glucose. In somepreferred embodiment, one or several of the other parameters are as wellconsidered with their margins of error. Covering preferably theclinically relevant range of preprandial blood glucose values (30-330mg/dl), the device simulates the postprandial blood glucose values asoutcome according to a treatment algorithm. In some embodiments, thedevice can then give a suggestion of treatment based on the postprandialglucose. Thus, it can help avoid reaching a critical point by givingadvice and/or performing functions that avoid reaching a critical point.

The present invention is further manifested by a software program and/ora data carrier including a program that is provided with the featuresthat it includes as parameters: a) preprandial measurement, b) effect ofcarbohydrate portions (CARB-P) on maximum glucose increase, c) patientestimate of carbohydrate amounts in food, d) effect of insulin onmaximum glucose decrease, and/or e) insulin dosage. The program analyzes(for example in 1 mg/dl steps) the maximum effect of the aboveparameters including the margins of error at least of the parameterpreprandial glucose on postprandial glucose. In some embodiments one orseveral of the parameters are considered with their margins of error. Insome embodiments, the present inventon relates to or covers theclinically relevant range of preprandial blood glucose values (30-330mg/dl). In some embodiments, the program simulates the postprandialblood glucose values as outcome according to a treatment algorithm.

In some preferred embodiments of the present invention an error is aswell taken into account for one or several of:

-   -   effect of carbohydrate-portion on maximum glucose incrase,        preferably blood glucose increase,    -   estimate of carbohydrate amount in meal    -   the effect of prandial insulin on maximum glucose decrease,        preferably blood glucose decrease, and    -   insulin dosage.

In a further preferred embodiment of the present invention postprandialglucose is determined for different ranges of preprandial glucosevalues, in some preferred embodiments blood glucose values, according tothe therapeutic scheme and the result is displayed as postprandialglucose (e.g., blood glucose) over preprandial glucose. In a furtherpreferred embodiment it is determined whether a critical point isreached by exceeding a lower limit for glucose or by exceeding an upperlimit for glucose, for example, in some preferred embodiments, bloodglucose.

In some preferred embodiments, the therapeutic scheme includes acarbohydrate self-adjustment in relation to preprandial blood glucose(BG) according to the relation: BG (mg/dl): <40 40-60 61-120 121-160161-200 201-240 241-300 301-360 CARB-P (n): X+2 X+1 X X−1 X−2 X−3 X−4X−5 wherein X equals the number of carbohydrate portions (X=1, 2, 3, 4or 5) for the blood glucose-range of 61-120 mg/dl.

In some embodiments, it is further preferred that the therapeutic schemeincludes a preprandial insulin dose self-adjustment according to therelation:

BG (mg/dl): <61 61-80 81-120 121-160 161-200 201-240 241-300 301-360Ins.-Dose (U): 0 −1Y Y +1Y +2Y +3Y +4Y +5Y wherein Y equals e.g. 1 unitinsulin per 1 CARB-P for the blood glucose range of 81-120 mg/dl.

In some embodiments, the present invention further comprises an errorgrid for the evaluation of measurement errors of blood glucose meters orcontinuous glucose monitors.

In some embodiments, the present invention further comprises a methodand/or device, e.g., a blood glucose meter, a continuous blood glucosemonitor or an insulin pump, wherein on the basis of at least one resultof the analysis of blood glucose at least one result, treatmentinformation or advice is given and wherein the result or advice is givendepending on the measurement error.

In some preferred embodiments of the present invention, the device is aportable device and is provided for measuring the blood glucose value ofa patient. In some embodiments, the device and/or method may be adaptedto display results, information or advice in a first measurement rangeor several first measurement ranges despite the measurement error, andmay be adapted to inhibit the display of results, information or adviceor display results, information or advice in a different mode in asecond measurement range or in several measurement ranges depending onthe measurement error. The display may be on the device or separatetherefrom and may be in wire or wireless connection with the device. Thedevice may comprise at least one movement sensor and the display may beactivated or inhibited dependent on a signal from the movement sensor.In some embodiments, the device comprises or is part of a system, toolor program as described herein, or has incorporated therein a system,tool or program as described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows parts of a screenshot depicting a first embodiment of thepresent invention;

FIG. 2 is a list of some of the parameters of a system or tool accordingto an embodiment of the present invention;

FIG. 3 is a table of the margins of error for the parameters of FIG. 2;

FIG. 4 is a diagram generated by an embodiment of the system, tool orprogram according to the present invention with zero error of allparameters;

FIG. 5 is a diagram as in FIG. 4 but with a +20% error of preprandialself-monitored blood glucose;

FIG. 6 is a diagram as in FIG. 5 with an error of 12% for theself-monitored blood glucose;

FIG. 7 is a diagram as in FIG. 5, but with an error of +25%;

FIG. 8 is a diagram as in FIG. 5, but with an error of +40%;

FIG. 9 is a table of parameter errors leading to a critical point inpostprandial blood glucose;

FIG. 10 depicts a known error grid model for judging acceptance ofmeasurement errors;

FIG. 11 depicts a new error grid model in accordance with the presentinvention;

FIG. 12 depicts the new error grid model used to measure the quality ofblood glucose measurements;

FIG. 13 depicts the new error grid model in comparison with the knownEGA model

DETAILED DESCRIPTION

With regard to fastening, mounting, attaching or connecting componentsof the present invention, unless specifically described as otherwise,conventional mechanical fasteners and methods may be used. Otherappropriate fastening or attachment methods include adhesives, weldingand soldering, the latter particularly with regard to the electricaland/or processing feature(s) of the invention, if any. In embodimentswith electrical features or components, suitable electrical componentsand circuitry, wires, wireless components, chips, boards, software,microprocessors, inputs, outputs, displays, control components, etc. maybe used. Generally, unless otherwise indicated, the materials for makingthe invention and/or its components may be selected from appropriatematerials such as metal, metallic alloys, ceramics, plastics, etc.

FIG. 1 shows a screenshot of one preferred embodiment of the presentinvention. As explained above, the invention can be embodied as asystem, a tool, a device, e.g. a glucose meter, and/or as a program. Allthese embodiments are encompassed when the present invention isexplained in the following, and the present invention may sometimes bereferred to as the or a Diabetes Error Test Model (DETM).

One preferred DETM calculates the postprandial blood glucose value. Itdoes not show a blood glucose (BG) curve over time, but focuses mainlyon the maximum effect resulting from insulin and carbohydrates consumed.However, these are not the only factors contributing to the BG result.There are numerous factors that affect the postprandial BG. Thefollowing are taken into account in the DETM and are shown in FIG. 2 asparameters that can be set. FIG. 3 shows the margins of error that areused in the present embodiment of the invention. The parameters can beset in the shown example by entering values in the fields and by movingthe shown slide input means (FIG. 1). Of course, in other embodiments ofthe invention, for example in a device being a blood glucose meter or acontinuous glucose monitor, parameters will be either measured directly,such as preprandial blood glucose or be entered via input means on thedevice or being stored beforehand. The parameters shown in FIGS. 1 and 2are: a) The pre-prandial blood glucose (BG) being in the range of 30mg/dl to 330 mg/dl which has actually been measured preprandial by adevice for self-monitoring of blood glucose, for example with a stripblood glucose meter; b) the variability or effect of a carbohydrateportion, giving the blood glucose increase in mg/dl of one carbohydrateportion and being settable between 20 mg/dl and 80 mg/dl; c) the amountof carbohydrate portions the patients aims or estimates to eat (C-P)with a value of 1 to 5; d) the variability or effect of the insulin,giving the blood glucose decrease in mg/dl for a unit of insulin andbeing settable between 30 mg/dl and 50 mg/dl; and e) the insulin dosage.

FIG. 3 shows the margin of error for the parameters: a) the error in %with which the pre-prandial glucose concentration has been measured,with a range of −50% to +50% error (0% meaning no error); b) the erroror variability of the effect of the carbohydrate effect with 45 mg/dl asnormal value and an error of up to 80 mg/dl and down to 20 mg/dl; c) theerror in estimating the desired amount of carbohydrate portions in %between 40% and 200% and wherein 100% means no error in estimating bythe person with diabetes; d) the error or variability of the glucoseconcentration decrease by the insulin with a value of 40 mg/dl aserrorless value and highest and lowest error values of 50 mg/dl and 30mg/dl; and e) the error in dosing the correct amount of insulin in % andbeing settable between −25% and +50% wherein 0% means no error indosing.

In one preferred embodiment, the preferred treatment algorithm used inthe DETM is based on the clinical experience of the German DiabetesResearch Institute/German Diabetes Centre at theHeinrich-Heine-University of Duesseldorf and can be shown in table 1 andtable 2:

TABLE 1 Carbohydrate Self-adjustment in relation to pre-prandial BG: BG(mg/dl) <40 40-60 61-120 121-160 161-200 201-240 241-300 301-360 CARB-P(n) X + 2 X + 1 X X − 1 X − 2 X − 3 X − 4 X − 5 (Base: X number ofCARB-P (X = 1, 2, 3, 4 or 5) for BG-range 61-120 mg/dl)

TABLE 2 Pre-prandial Analog-Insulin Dose Self-adjustment BG (mg/dl) <6161-80 81-120 121-160 161-200 201-240 241-300 301-360 Ins.-Dose (U) 0 −1YY +1Y +2Y +3Y +4Y +5Y (Base: Y; e.g. 1 U/1 CARB-P for BG range 81-120mg/dl)

So, as an example of table 1 if in the blood glucose range of 61 to 120mg/dl a carbohydrate portion X of 1 to 5 is considered, this portionvalue will be adjusted to X−2 when the self-monitored blood glucosevalue is in the range of 161 to 200 mg/dl.

As an example of table 2, one unit of insulin (Y) is considered percarbohydrate portion if the self-monitored pre-prandial blood glucosevalue is in the range of 81 to 120 mg/dl but is made higher by +2 unitsif the blood glucose value is in the range of 161 to 200 mg/dl. Othertreatment algorithms could be used as well but the preferred algorithmis simple to implement since it is based on addition and subtraction ofcarbohydrate portions and insulin units for the shown ranges ofpreprandial self-monitored blood glucose. The ranges can be shifted tovary the algorithm and fractions of insulin units or carbohydrateportion could be used.

The aim of the treatment algorithm is to lead the patient's BG tonormoglycemia (60-160 mg/dl), whole blood. This range from 60-160 mg/dlis called target range. Of course it can be chosen to either adjustusing insulin or carbohydrates for BG>120 mg/dl. As an example acalculation based on the preferred treatment algorithm can be shown asfollows wherein the error of the self-monitored blood glucose is takeninto account by 10% and for example additionally the errors ofcarbohydrate and insulin effects could be considered but are set to zero% in this calculation, so the blood glucose increase of one portioncarbohydrates is 45 mg/dl and the decrease caused by the insulin is 40mg/dl:

-   -   True BG: 120    -   Measurement error: 10%    -   Effect CARP-P: 45    -   Effect insulin: 40    -   Error: 0%    -   Number of carb. portions: 5 Carp-P    -   True BG with error (measured blood glucose): 120 mg/dl×1,1=132        mg/dl

According to the treatment algorithm above 132 mg/dl leads to:

either 1 CARP-P less than intended is eaten (X−1) since the bloodglucose is now in the range of 121 to 160 and thus 120 mg/dl+(4*45mg/dl)−(5*40 mg/dl)=100 mg/dl and thus normoglycemia; or

1 additional unit insulin is administered (+1Y) if the intendedcarbohydrate portion is eaten since the blood glucose is now in therange of 121 to 160, and thus 120 mg/dl+(5*45)−(6*40)=105 mg/dl and thusnormoglycemia.

The system, tool, device and program according to the present inventionallows the calculation of the postprandial blood glucose as the outcomeof the pre-prandial blood glucose if the therapeutic action is takenaccording to the preferred algorithm (or according to anotheralgorithm). In some preferred embodiments, the values of postprandialglucose concentration are then displayed over pre-prandial measuredglucose concentration. At first, the effects of BG measurement errorsare evaluated while all other parameters are kept at 0% error.

FIG. 4 shows postprandial glucose concentration kept within the targetrange (shown by the horizontal lines at 60 mg/dl and 160 mg/dlpostprandial glucose concentration). As an indicator for the error ofthe self-monitored glucose concentration the 0% error line isadditionally shown which is usually not the case, so that, in somepreferred embodiments, a preferred display shows only measuredpre-prandial blood glucose values on the horizontal x-axis andcalculated postprandial blood glucose values on the lefthand verticaly-axis.

The DETM-program can display all variables relevant in the calculationof the glucose concentration outcome in an additional window not shownin FIG. 1. Among those are the final carbohydrate portions the patientswill eat after considering his current situation (C-P), the insulin heneeds to apply (Y IU) and, of course, the glucose concentration result(BG_R). The “interesting” values can be checked to be displayed in agraph as, for example, shown in FIG. 4.

The graph can display the postprandial glucose concentration in relationto one changing variable. The other variables are kept constant to theset value. In some preferred embodiments, the preferred graph used mostoften is the shown relation between the pre-prandial (reference) glucoseconcentration (with values between 30 and 330 mg/dl) and thepostprandial outcome.

In the graph of FIG. 4 it can be seen that with all parameters kept at0% error all preprandial values from 30-330 mg/dl will result inpostprandial values between 60 and 160 mg/dl target range). Thecharacteristic saw tooth nature of this graph and the following graphsis a result of the stepwise nature from the treatment algorithm. In someembodiments, involving a different treatment algorithm, the resultantgraph and/or display may be different from that depicted.

FIG. 5 shows that a glucose concentration error of +20% (classified bye.g. the Error Grid Analysis (EGA) as related to zone A and thus so faras allowable, see further below) results as postprandial “outcome” innormoglycemia if preprandial glucose concentration values are in theranges of 30-130 mg/dl and 260-330 mg/dl. However, the postprandialglucose concentration results unexpectedly in hypoglycemia ifpreprandial erroneous BG values are between 131 and 259 mg/dl. In thisrange the critical point where the target range is left for hypoglycemiais already reached at a BG measurement error of +12% as can be shown inFIG. 6. Thus, a device such as a blood glucose meter or an insulin pumpwill be able to display useful values or therapeutic advice if thepreprandial values are in the range of 30-130 mg/dl and will actaccordingly while on the other hand such a device will inhibit thedisplay of results in the range of 131-259 mg/di or will inhibitdisplaying therapeutical advice or will give a warning. FIGS. 7 and 8show postprandial glucose values for other error percentages of theself-monitored glucose. FIG. 7 shows the postprandial blood glucose todecrease into hypoglycemia due to a preprandial self-monitored glucosemeasurement with an error of +25% (with all other errors of the systemkept to 0%). FIG. 8 shows a decrease into hypoglycemia due to apreprandial error of 40%.

The DETM system, tool, device and program provide for and/or allow thecharacterization of the relevance of errors of parameters affecting BGon postprandial BG outcome. It describes in detail the effects ofpotential errors of parameters affecting glucose concentration onpostprandial glucose values within the clinically relevant glucoserange. It evaluates the clinical relevance of these errors and presentsa detailed risk assessment with the focus on postprandial outcome. Insome preferred embodiments, it is therefore preferably used in or as aneducational tool(s) for explaining the relations to people withdiabetes. In some preferred embodiments, it is used in devices fordiabetes care. For example, when used in a blood glucose meter, thesystem, tool or program will know the measurement error of the deviceand can therefore calculate the postprandial blood glucose and can givea warning if a critical point is reached. The device can further give acorrected treatment advice or information if it detects that, based onthe self-monitored blood glucose value, the error and other parameters,a critical point would be reached for the postprandial blood glucosevalue.

The Critical Point (CP): A Critical Point is reached if (preprandial)normoglycemia turns into (postprandial) hypo- or hyperglycemia or(preprandial) hyperglycemia turns into (postprandial) hypoglycemia or(preprandial) hypoglycemia turns into (postprandial) hyperglycemia. Forexample if the glucose measurement error is 11% this leads for thepreprandial glucose value of 219 mg/dl to a postprandial value of 59mg/dl (outside the target range). As 11% is the lowest value for theglucose measurement error to result in at least one value outside thetarget range this is called the Critical Point. FIG. 9 shows a table ofcritical points reached by parameter errors.

The treatment algorithm can be extended to Continuous Glucose Monitoring(CGM). The following assumptions are made for possible glucose changes:

Very Fast glucose increase >+2 mg/dl/min UU Fast +(1-2) mg/dl/min U Slowchanges <±1 mg/dl/min = Fast decrease −(1-2) mg/dl/min D Very Fastdecrease >−2 mg/dl/mim DD

glucose-Trend (mg/dl/min) glucose-Change(mg/dl) in 30 minutes mean rangemean range UU +3.0 +(2.1→3.9) → +45 +(31→59) U +1.5 +(1.0→2.0) → +23+(15→30) = ±0 −0.9→+0.9 → ±0 −14→+14 D −1.5 −(1.0→2.0) → −23 −(15→30) DD−3.0 −(2.1→3.9) → −45 −(31→59)This leads to the following treatment algorithms for adapting theinsulin units:

Glucose (mg/dl) Trend <61 61-80 81-120 121-160 161-200 201-240 241-300301-360 UU 0   Y +1Y +2Y +3Y +4Y +5Y +6Y U 0 −1Y   Y +1Y +2Y +3Y +4Y +5Y= 0 −1Y   Y +1Y +2Y +3Y +4Y +5Y D 0 −2Y −1Y   Y +1Y +2Y +3Y +4Y DD 0 −3Y−2Y −1Y   Y +1Y +2Y +3YIn the DETM-program, tool, system or device the CGM-algorithms can beused for any calculation made. In particular, the device in this case ofalgorithm is a continuously measuring glucose monitor.

Another aspect of the present invention is that by using the DETM modeland algorithms, an error grid model similar to the EGA can becalculated, called hereinafter the EAA. FIG. 10 shows the EGA as known.[Joan L. Parkes, Scott Pardo, Stephen 1. Slatin, Barry H. Ginsberg, “Anew consensus Error Grid to evaluate the clinical significance ofinaccuracies in the measurement of blood glucose”, Diabetes Care, Vol23, No. 8, pages 1143-1148, August 2000].

In some preferred embodiments, by using the DETM system, tool andprogram with preferred algorithms, an error grid model comparable to theEGA can be calculated.

The target range is amended with an acceptance range (50-200 mg/dl); thetarget range is the equivalent to EGA zone A; the acceptance range isthe equivalent to EGA zone B; for the EAA it is calculated whichmeasurement error at which pre-prandial glucose value leads to apost-prandial BG value outside the target/acceptance range.

The result is a relation between preprandial reference glucose andpreprandial self-monitored glucose as shown in FIG. 11. The full linesrepresent the target range, the dotted lines the acceptance range. TheEAA can now be used to measure the quality of glucose measurements byprojecting the reference value and self-measurement value into the gridas shown in FIG. 12. Points outside the full/dotted lines mean that if apatient measured this value (with the corresponding reference value)his/her glucose concentration would result in hypo/hyperglycemia afterapplying his treatment algorithm. In this figure most of the points liebetween the lines, but several points are outside (above). This meansthat using this glucose meter, the patient is in danger of ending up inhypoglycemia.

In order to evaluate the exact risk, the system, tool and program inaccordance with the present invention offers the option of calculatingboth EAA and EGA as shown in FIG. 13. In this calculation it can be seenthat 9% of the points are outside the acceptance range. Interestingly,no point is outside zone A of the EGA. This means that, according to theEGA, this measurement device is perfect, while according to the EAA itis unusable. The EGA can be painted into the EAA as shown to provide anoptical visualization.

Notes and considerations: the DETM and treatment algorithms arecalibrated to whole blood. Nevertheless the system, tools, devices andthe program in accordance with the present invention may offer theoption of switching to plasma. The DETM focuses on the BG-outcome afterfood intake and insulin administration (with several side effects).

The EAA focuses on evaluating the quality of a measurement device. Thisquality depends on the treatment algorithm used (which can be adapted inthe DETM-program) Continuous glucose monitoring is implemented usingslight modifications to the standard treatment algorithm withoutbreaking the scheme

Any or all parameters and/or features associated with the presentinvention can be combined. This means that, for example, all EAAcalculations can be performed for higher insulin impact then usual.

In some preferred embodiments, the DETM-program has a database or memoryoperably coupled, linked or attached so that results from tests ofmeasurement devices can be stored, selected and/or transmitted easily.

The measurement error of an analytical system such as a blood glucosemeter or a continuous glucose monitor influences the usefulness andsignificance of the analytical result. If the measured glucose value isoutside of a physiologically preferable concentration, a therapeuticaction is initiated with the aim of restoring the physiologicallypreferred state. In case of diabetes mellitus therapeuticalinterventions such as administering insulin or carbohydrates are takento bring the concentration of glucose back to normoglycemia. Theanalytical result can be displayed or otherwise presented as numericalvalue or as therapeutic advice based on the measurement which can be asingle measurement or a measurement and a consideration of earliermeasurements as in continuous glucose monitoring.

The therapeutic intervention depends on the concentration orconcentration range of the glucose value and the target range fornormoglycemia. In the present invention the display or presentation oftherapeutic advice or information is made dependent on the outcome ofthe glucose value (e.g. the postprandial value) which, on the otherhand, depends on the error of the measurement as explained above. Inparticular, in some embodiments advice is given or informationcommunicated only if the above explained system, tool or program detectsthat postprandial glucose is within the target range for the actualmeasurement range.

Accordingly, since the display of a measured value or advice, e.g.,therapeutic advice, is given under consideration of the measurementerror and its relevance for the later reached blood glucose value, it ispossible to communicate or present therapeutic advice or a measurementdisplay that is informative and correct for the user. It can be takeninto account by the device that a measurement is within a range thatallows advice to be presented or communicated despite the measurementerror or is within a range that leads to a critical point so that noadvice or modified advice has to be given.

An advantage of the present invention is therefore that in those rangesof glucose where correct therapy advice can be given despite a largemeasurement error such advice will be given. On the other hand, in thoseranges where it is necessary to have a low error for giving a correcttherapy advice such advice can be inhibited or modified or replaced by awarning. The display may be presented or communicated in any suitableform, e.g. either directly on a device, or by wireless (infrared,radiofrequencies) or wirebound data connection with a device.

For example, if the device is a continuously monitoring glucose devicethat reacts on movements of the wearer in such a way that movements mayincrease the measurement error, it may be preferred to have a movementsensor included in the device so that the error by movement can beincluded in the above explained calculation by adding a further errorparameter.

While preferred embodiments of the present invention are shown anddescribed, it should be understood that the invention is not limitedthereto but may be otherwise variously embodied and practiced within thescope of the following claims.

1-37. (canceled)
 38. A device wherein, on the basis of at least oneresult of the analysis of glucose, at least one of a result, advice orinformation is provided by the device or a peripheral device, andwherein the result, advice or information is provided depending on ameasurement error.
 39. The device of claim 38, wherein the device isportable and is provided for measuring the glucose value of a patient.40. The device according to claim 38, wherein the device is adapted todisplay a result, advice or information in a first measurement range orseveral first measurement ranges despite the measurement error, and isadapted to inhibit the display of a result, advice or information in asecond measurement range or in several measurement ranges depending onthe measurement error.
 41. The device according to claim 38, furthercomprising an operably coupled display in one of wired or wirelessconnection with the device.
 42. The device according to claim 41,further comprising at least one movement sensor wherein the display maybe activated or inhibited dependent on a signal from the movementsensor.
 43. The device according to claim 38, said device adapted totake into account at least one of: a preprandial glucose concentrationmeasurement by self-monitoring of glucose; an effect ofcarbohydrate-portion on maximum glucose incrase; an estimate ofcarbohydrate amount in a meal; an effect of prandial insulin on maximumglucose decrease; and an insulin dosage; wherein a margin of error forthe self-monitored preprandial glucose is taken into account andpostprandial glucose values are calculated based on a therapeutic actionscheme.
 44. The device according to claim 43, further comprising takinginto account an error associated with at least one of: the effect ofcarbohydrate-portion on maximum glucose concentration increase; theestimate of carbohydrate amount in a meal; the effect of prandialinsulin on maximum glucose concentration decrease, and the insulindosage.
 45. The device according to claim 44, wherein postprandialglucose concentration is determined for different ranges of preprandialglucose concentration values according to the therapeutic scheme. 46.The device according to claim 45, wherein a result is displayed aspostprandial blood glucose over preprandial blood glucose.
 47. Thedevice according to claim 46, wherein the device is one of a bloodglucose meter, a continuous glucose monitor or an insulin pump.
 48. Thedevice according to claim 43, adapted for glucose measurement or glucosemonitoring in blood or any tissue compartment, tissues, body fluid orinterstitial fluid.
 49. (canceled)